This invention concerns new oxazolines that are useful as insecticides and acaricides. More particularly, the present invention concerns 2-(2,6-disubstituted phenyl)-4-aryl-5-alkyl-1,3-oxazoline compounds and their stereoisomers. This invention also includes new synthetic procedures and intermediates for preparing the compounds, pesticide compositions containing the compounds, and methods of controlling insects and mites using the compounds.
There is an acute need for new insecticides and acaricides. Insects and mites are developing resistance to the insecticides and acaricides in current use. At least 400 species of arthropods are resistant to one or more insecticides. The development of resistance to some of the older insecticides, such as DDT, the carbamates, and the organophosphates, is well known. But resistance has even developed to some of the newer pyrethroid insecticides and acaricides. Therefore a need exists for new insecticides and acaricides, and particularly for compounds that have new or atypical modes of action.
2-(Substituted-phenyl)-1,3-oxazolines with insecticidal activity are disclosed in JP 4-89484, EP 0345775-A1, EP 0432661-A2, EP 0553623-A1, WO 99/01443, WO 99/23081 and WO 98/47881. 2-Aryl- and 2-heteroaryl-1,3-oxazolines with acaricidal and insecticidal activity are disclosed in JP 6-145169 and WO 99/65901. Arthropocidal 2-(substituted-phenyl)-1,3-oxazolines are disclosed in WO 93/24470. To the applicants"" knowledge, only one oxazoline product, etoxazole, has been developed as a commercial acaricide. It would be highly desirable to discover related compounds of this mode of action that are more potent, more selective or of broader spectrum in their activity and/or that have improved toxicological and environmental properties.
This invention provides novel 2-(2,6-disubstituted phenyl)-4-aryl-5-alkyl-1,3-oxazoline derivatives especially useful for the control of insects and mites.
More specifically, the invention provides novel insecticidally active compounds of the formula (I) 
wherein
R1 is (C1-C3) alkyl or (C1-C3) haloalkyl;
R2 and R3 are independently H, halogen, (C1-C3) alkyl, (C1-C3) haloalkyl, (C1-C3) alkoxy or (C1-C3) haloalkoxy;
Q is a group selected from 
R4 is H, halogen, hydroxy, (C1-C6) alkyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1-C6) haloalkoxy, (C1-C6) alkoxyalkyl, (C1-C6) alkoxyalkoxy, (C2-C6) alkenyl, (C2-C6) haloalkenyl, CN, NO2, CO2R6, CON(R6)2, S(O)mR6, SCN, xe2x80x94CH2OR6, xe2x80x94CH2SR6, xe2x80x94CH2NR6R6, xe2x80x94OCH2R6, xe2x80x94SCH2R6, xe2x80x94NR6CH2R6, 
R5 represents 
R6 is H, (C1-C6) alkyl, (C1-C6) haloalkyl, (C2-C6) alkenyl, (C2-C6) alkynyl, phenyl, or substituted phenyl;
R7 and R8 are independently H, halo, (C1-C6) alkyl, (C1-C6) haloalkyl, (C1-C6) alkoxy or (C1-C6) haloalkoxy;
X and Y are independently Cl, F, methyl, halomethyl, methoxy, or halomethoxy;
m is 0, 1, or 2; and
Z is a direct bond, CH2, CH2CH2, O or S
or a phytologically acceptable acid addition salt or N-oxide thereof.
Preferred compounds of formula (I) include the following classes:
(1) Compounds of formula (I) wherein X and Y are both halogen.
(2) Compounds of class (1) wherein X and Y are both F.
(3) Compounds of formula (I) wherein R2 and R3 are H.
(4) Compounds of formula (I) wherein R4 is H, halogen, (C1-C6) alkyl, (C1-C6) haloalkyl, (C1-C6) alkoxy or (C1-C6) haloalkoxy.
(5) Compounds of formula (I) wherein Q is 
(6) Compounds of class (5) wherein R5 is 
(7) Compounds of formula (I), and particularly compounds of class (6) as defined above, wherein Z is a direct bond.
(8) Compounds of formula (I) wherein R1 is methyl.
It will be appreciated by those skilled in the art that the most preferred compounds are generally those which are comprised of various combinations of the above preferred classes.
Particularly preferred compounds are of formula (Ia) 
The invention also provides new processes and intermediates for preparing compounds of formula (I) as well as new compositions and methods of use, which will be described in detail hereinafter.
Throughout this document, all temperatures are given in degrees Celsius, and all percentages are weight percentages unless otherwise stated.
Unless specifically limited otherwise, the terms xe2x80x9calkylxe2x80x9d, xe2x80x9calkenylxe2x80x9d and xe2x80x9calkynylxe2x80x9d, as well as derivative terms such as xe2x80x9calkoxyxe2x80x9d and xe2x80x9calkanoylxe2x80x9d, as used herein, include within their scope straight chain, branched chain and cyclic moieties. The terms xe2x80x9calkenylxe2x80x9d and xe2x80x9calkynylxe2x80x9d are intended to include one or more unsaturated bonds.
Unless specifically limited otherwise, the term xe2x80x9chalogenxe2x80x9d, as well as derivative terms such as xe2x80x9chaloxe2x80x9d, as used herein, refer to fluorine, chlorine, bromine, and iodine. Preferred halogens are fluorine and chlorine.
The terms xe2x80x9chalomethylxe2x80x9d, xe2x80x9chaloalkylxe2x80x9d, and xe2x80x9chaloalkenylxe2x80x9d refer to methyl, alkyl, and alkenyl groups substituted with from one up to the maximum possible number of halo atoms. The terms xe2x80x9chalomethoxyxe2x80x9d and xe2x80x9chaloalkoxyxe2x80x9d refer to methoxy and alkoxy groups substituted with from one up to the maximum possible number of halo atoms.
The terms xe2x80x9csubstituted pyridyl,xe2x80x9d xe2x80x9csubstituted isoxazolyl,xe2x80x9d xe2x80x9csubstituted thienyl,xe2x80x9d and xe2x80x9csubstituted thiazolylxe2x80x9d refer to the ring system substituted with one or more groups independently selected from halo, (C1-C4) alkyl, (C1-C4) haloalkyl, CN, NO2, phenyl, (C1-C4) alkoxy, or (C1-C4) haloalkoxy.
The term xe2x80x9csubstituted phenylxe2x80x9d refers to a phenyl group substituted with one or more groups independently selected from halo, (C1-C10) alkyl, (C1-C7) haloalkyl, (C1-C7) hydroxyalkyl, (C1-C7) alkoxy, (C1-C7) haloalkoxy, phenoxy, phenyl, NO2, OH, CN, (C1-C4) alkanoyl, benzoyl, (C1-C4) alkanoyloxy, (C1-C4) alkoxycarbonyl, phenoxycarbonyl, or benzoyloxy.
Unless otherwise indicated, when it is stated that a group may be substituted with one or more substituents selected from an identified class, it is intended that the substituents may be independently selected from the class, provided that the substituents are sterically compatible and the rules of chemical bonding and strain energy are satisfied.
Relative to the oxazoline ring, the compounds of this invention can exist as one or more stereoisomers. The various stereoisomers include geometric isomers, diastereomers and enantiomers. Thus the compounds of the present invention include racemic mixtures, individual stereoisomers and optically active mixtures. For example, for compounds of the formula (Ia) 
the following stereoisomers are possible: 
It will be appreciated by those skilled in the art that one stereoisomer may be more active than the others. Individual stereoisomers and optically active mixtures may be obtained by selective synthetic procedures, by conventional synthetic procedures using resolved starting materials or by conventional resolution procedures.
Compounds of formula (I), in particular diastereomers Syn (I) and Anti (I) can be prepared by the method illustrated in Scheme A: 
wherein R1, Q, X and Y are as defined in formula (I).
In step a of Scheme A, the compound of formula (A) is reacted with an aminoalcohol (D) to afford a compound of formula (C). 1,2-Dichloroethane is the preferred solvent, however other polar aprotic solvents such as pyridine or THF can also be used.
In step b of Scheme A the N-amidealcohol of formula (C) can be reacted with either (diethylamino)sulfur trifluoride (DAST) or with thionyl chloride to provide the products of formula Syn (I) and Anti (I) which can be separated using chromatographic techniques. The DAST reaction is carried out in dichloromethane or 1,2-dichloroethane at a temperature in the range from xe2x88x9278xc2x0 C. to ambient temperature. The thionyl chloride reaction is carried out in dichloromethane or 1,2-dichloroethane at a temperature in the range from 0xc2x0 C. to ambient temperature.
Alternatively, when Q represents 
compounds of formula (I), in particular diastereomers Syn (Ic) and Anti (Ic), can be prepared by the method shown in Scheme B: 
wherein R1, Q, R4, R5, X and Y are as defined in formula (I).
In step a of Scheme B, oxazoline of formula Syn (Ib)/Anti (Ib) is reacted under standard Suzuki coupling reaction conditions with an appropriately substituted R5-boronic acid to provide the product of formula Syn (Ic)/Anti (Ic) which can be separated using chromatographic techniques. The coupling reaction is carried out in an acetonitrile/water mixture, or ethanol, at a temperature in the range from ambient to refluxing temperature. Catalytic amounts of dichlorobis(triphenylphosphine)palladium(II) or tetrakis(triphenylphosphine)palladium(O) are typically used for coupling, however other Pd(II) or Pd(O) catalysts can also be used. Typically sodium carbonate was used as base in the coupling reaction but other inorganic or organic bases such as potassium carbonate or triethylamine can also be used.
Alternatively, compounds of formula (I), in particular racemic Syn (I) and Anti (I) can be prepared by the method illustrated in Scheme C: 
wherein R1, Q, X and Y are as defined in formula (I).
In step a of Scheme C, the compound of formula (A) is reacted with an aminoalcohol (D) or (E) to afford a compound of formula (C) or (B). 1,2-Dichloroethane is the preferred solvent, however other polar aprotic solvents such as pyridine or THF can also be used.
The ring closure step b of Scheme C is similar to step b of Scheme A and provides the products of formula Syn (I) and Anti (I) which can be separated using chromatographic techniques.
Alternatively, when Q represents 
compounds of formula (I), in particular diastereomers Syn (Ic) and Anti (Ic), can be prepared by the method shown in Scheme D: 
wherein R1, Q, R4, R5, X and Y are as defined in formula (I).
The Suzuki coupling step a of Scheme D is similar to step a of Scheme B and provides products of formula Syn (Ic) and Anti (Ic) which can be separated using chromatographic techniques.
Compounds of formula (I), in particular enantiomers Syn (If) and Syn (Ig) and Anti (If) and Anti (Ig), can be prepared by the method shown in Scheme E: 
wherein R1, Q, R4, R5, X and Y are as defined in formula (I).
The Suzuki coupling step a of Scheme E is similar to step a of Scheme B and provides products of formula Syn (If) and Syn (Ig) and Anti (If) and Anti (Ig) which can be purified using chromatographic techniques.
Compounds of formula (D) can be prepared by the method illustrated in Scheme F: 
wherein R is R4 and/or R5 and R1, R4 and R5 are as defined in Formula (I).
In step a of Scheme F, the compound of formula (F) is reacted with a mixture of potassium acetate and tetrabutylammonium chloride at refluxing temperature of dichloroethane to afford a compound of formula (G). Dichloroethane is the preferred solvent, however other chlorinated solvents such as dichloromethane or carbon tetrachloride can be used. Alternatively the transformation can also be carried out using inorganic acetates such as sodium acetate with other phase transfer catalysts such as tetrabutylammonium bromide or iodide.
In step b of Scheme F, the compound of formula (G) is reacted with potassium acetate in ethanol followed by treatment with methoxylamine hydrochloride to provide the compound of formula (H).
In step c of Scheme F, the compound of formula (H) is reacted with a reducing agent such as sodium borohydride in trifluoroacetic acid to provide the compound of formula (D) in an organic solvent such as tetrahydrofuran. The reaction can be performed at ambient to refluxing temperature. The product can be isolated as a salt, preferably as the HCl or oxalate salt.